Xu Chang, Zhang Chunhong, Wang Haowen, Yang Han, Li Gang, Fei Zhenghua, Li Wenfeng
Department of Colorectal Surgery.
Department of Pharmacy.
Onco Targets Ther. 2017 Mar 30;10:1933-1939. doi: 10.2147/OTT.S118346. eCollection 2017.
Previous studies used enumerated circulating tumor cells (CTCs) to predict prognosis and therapeutic effect in several types of cancers. However, increasing evidence showed that only enumerated CTCs were not enough to reflect the heterogeneity of tumors. Therefore, we classified different metastasis potentials of CTCs from colorectal cancer (CRC) patients to improve the accuracy of prognosis by CTCs.
Blood samples were collected from 45 primary CRC patients. CTCs were enriched by blood filtration, and the RNA in situ hybridization method was used to identify and discriminate subgroups of CTCs. Later, FAM172A expression in individual CTCs was measured.
Three CTC subgroups (epithelial/biophenotypic/mesenchymal CTCs) were identified using epithelial-mesenchymal transition markers. In our research, mesenchymal CTCs significantly increased along with tumor progression, including developing distant metastasis and vascular invasion. Furthermore, FAM172A expression rate in mesenchymal CTCs was significantly higher than that in epithelial CTCs, which suggested that FAM172A may correlate with tumor malignancy. This hypothesis was further verified by FAM172A expression in mesenchymal CTCs strictly related to tumor aggressiveness factors. Finally, we revealed that mesenchymal CTCs and FAM172A expression may predict high-risk subgroups in stage II CRC.
Our research proved that CTCs could serve as feasible surrogate samples to detect gene expression as a predictive biomarker for tumor evaluation.
以往的研究使用枚举循环肿瘤细胞(CTC)来预测几种癌症类型的预后和治疗效果。然而,越来越多的证据表明,仅枚举CTC不足以反映肿瘤的异质性。因此,我们对结直肠癌(CRC)患者的CTC不同转移潜能进行分类,以提高通过CTC进行预后评估的准确性。
收集45例原发性CRC患者的血样。通过血液过滤富集CTC,并使用RNA原位杂交方法识别和区分CTC亚组。随后,检测单个CTC中FAM172A的表达。
使用上皮-间质转化标志物鉴定出三个CTC亚组(上皮/双表型/间质CTC)。在我们的研究中,间质CTC随着肿瘤进展显著增加,包括发生远处转移和血管侵犯。此外,间质CTC中FAM172A的表达率显著高于上皮CTC,这表明FAM172A可能与肿瘤恶性程度相关。这一假设通过与肿瘤侵袭性因素密切相关的间质CTC中FAM172A的表达得到进一步验证。最后,我们发现间质CTC和FAM172A表达可能预测II期CRC中的高危亚组。
我们的研究证明,CTC可作为可行的替代样本,用于检测基因表达,作为肿瘤评估的预测生物标志物。